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The evidence for the impact of renal dysfunction in patients with diabetes mellitus (DM) and first cardiovascular diseases on mid-term adverse outcomes remain scarce. This study included the data of patients with DM having first atherosclerotic cardiovascular disease (ASCVD) or congestive heart failure (CHF) from the Taipei Medical University Clinical Research Database. A Cox proportional hazards regression model was used to assess the impact of chronic kidney disease (CKD) or end-stage renal disease (ESRD) on the 1-year mortality and recurrent ASCVD/CHF outcomes. We enrolled 21,320 patients with DM hospitalized for ASCVD or CHF; of them, 18,185, 2639, and 496 were assigned to the non-CKD, CKD, and ESRD groups, respectively. After propensity score matching, compared with the non-CKD group, the CKD and ESRD groups had higher mid-term all-cause mortality (adjusted hazard ratio 1.72 [95% confidence interval 1.48-1.99] and 2.77 [2.05-3.73], respectively), cardiovascular death (1.84 [1.44-2.35] and 1.87 [1.08-3.24], respectively), and recurrent hospitalization for ASCVD (1.44 [1.24-1.68] and 2.33 [1.69-3.23], respectively) and CHF (2.08 [1.75-2.47] and 1.50 [1.04-2.17], respectively). The advancing age was associated with mortality in CKD/ESRD groups. In CKD group, male sex was associated with all-cause mortality and recurrent ASCVD risk; the diuretics usage was associated with mortality and recurrent CHF risks. Our findings suggest that CKD and ESRD are significant risk factors for mid-term adverse outcomes in patients with DM and established cardiovascular diseases. Additionally, old age, male sex and diuretics usage requires attention. Further good quality studies are needed in the future.
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Enfermedades Cardiovasculares , Fallo Renal Crónico , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Anciano , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Persona de Mediana Edad , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/complicaciones , Factores de Riesgo , Modelos de Riesgos Proporcionales , Diabetes Mellitus/epidemiología , Taiwán/epidemiología , HospitalizaciónRESUMEN
Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids is associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact of pressure on the peritoneum remains unclear. In the present study, we hypothesized increased pressure is a potential contributing factor to peritoneal fibrosis and investigated the possible mechanisms. In vitro experiments found that pressurization led to a mesenchymal phenotype, the expression of fibrotic markers and inflammatory factors in human mesothelial MeT-5A cells. Pressure also increased cell proliferation and augmented cell migration potential in MeT-5A cells. The mouse PD model and human peritoneum equilibrium test (PET) data both showed a positive association between higher pressure and increased small solute transport, along with decreased net UF. Mechanistically, we found that significant upregulation of CD44 in mesothelial cells upon pressurization. Notably, the treatment of CD44 neutralizing antibodies prevented pressure-induced phenotypic changes in mesothelial cells, while a CD44 inhibitor oligo-fucoidan ameliorated pressure-induced peritoneal thickening, fibrosis, and inflammation in PD mice. To conclude, intraperitoneal pressure results in peritoneal fibrosis in PD via CD44-mediated mesothelial changes and inflammation. CD44 blockage can be utilized as a novel preventive approach for PD-related peritoneal fibrosis and UF failure.
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Receptores de Hialuranos , Diálisis Peritoneal , Fibrosis Peritoneal , Peritoneo , Transducción de Señal , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/patología , Animales , Ratones , Receptores de Hialuranos/metabolismo , Humanos , Peritoneo/patología , Peritoneo/metabolismo , Diálisis Peritoneal/efectos adversos , Modelos Animales de Enfermedad , Inflamación/metabolismo , Presión/efectos adversos , Masculino , Proliferación Celular , Transición Epitelial-Mesenquimal , Ratones Endogámicos C57BL , Línea Celular , Movimiento CelularRESUMEN
BACKGROUND: Optimal timing for initiating maintenance dialysis in patients with chronic kidney disease (CKD) stages 3-5 is challenging. This study aimed to develop and validate a machine learning (ML) model for early personalised prediction of maintenance dialysis initiation within 1-year and 3-year timeframes among patients with CKD stages 3-5. METHODS: Retrospective electronic health record data from the Taipei Medical University clinical research database were used. Newly diagnosed patients with CKD stages 3-5 between 2008 and 2017 were identified. The observation period spanned from the diagnosis of CKD stages 3-5 until the maintenance dialysis initiation or a maximum follow-up of 3 years. Predictive models were developed using patient demographics, comorbidities, laboratory data and medications. The dataset was divided into training and testing sets to ensure robust model performance. Model evaluation metrics, including area under the curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value and F1 score, were employed. RESULTS: A total of 6123 and 5279 patients were included for 1 year and 3 years of the model development. The artificial neural network demonstrated better performance in predicting maintenance dialysis initiation within 1 year and 3 years, with AUC values of 0.96 and 0.92, respectively. Important features such as baseline estimated glomerular filtration rate and albuminuria significantly contributed to the predictive model. CONCLUSION: This study demonstrates the efficacy of an ML approach in developing a highly predictive model for estimating the timing of maintenance dialysis initiation in patients with CKD stages 3-5. These findings have important implications for personalised treatment strategies, enabling improved clinical decision-making and potentially enhancing patient outcomes.
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Aprendizaje Automático , Diálisis Renal , Insuficiencia Renal Crónica , Humanos , Femenino , Masculino , Estudios Retrospectivos , Insuficiencia Renal Crónica/terapia , Persona de Mediana Edad , Anciano , Registros Electrónicos de Salud , Taiwán , Medicina de PrecisiónRESUMEN
In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, including male gender, older age, diabetes, coronary heart disease, stroke, heart failure, sepsis, and surgery. There was an extremely high mortality rate among the first unplanned dialysis patients in Taiwan. Less than 10% of these patients underwent continued dialysis during the 5-year follow-up period. This study highlighted the urgent need for interventions to improve patient outcomes.
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Diabetes Mellitus , Fallo Renal Crónico , Humanos , Masculino , Diálisis Renal/efectos adversos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Estudios de Cohortes , Factores de Riesgo , Diabetes Mellitus/etiología , Taiwán/epidemiología , Estudios RetrospectivosRESUMEN
The world healthcare system is actively seeking possible solutions for the rapid growth of kidney disease threats. The Taiwan Renal Data System (TWRDS) was central in assisting kidney health and care policymaking to reduce end-stage kidney disease incidence and mortality. This article summarizes the TWRDS framework, recent applications, and developments to provide new insights for some international researchers to promote planetary kidney health. The TWRDS originated in 1987 for the accreditation and quality monitoring of dialysis units and was connected with enriched health claim databases after the implementation of universal national health insurance in Taiwan in 1995. As a healthcare information centre, TWRDS has published annual reports forming indispensable instructions for renal care improvement since 2014. The TWRDS possesses three main functions: (1) kidney disease surveillance; (2) offering rich materials for research purposes; (3) achieving precision prevention and care through complex algorithms. In the new era, TWRDS can help build a more resilient society against communicable disease threats by integrating remote sensor techniques for developing future remote healthcare structures, as well as identifying kidney health inequity populations and promoting healthcare resources distributed equity. The global healthcare system is facing escalating burdens of non-communicable disease care due to the rapidly growing elderly population. Therefore, a considerable-scale data system is an essential decision-supportive tool in promoting an evidence-based, resilient, sustainable, equity care environment. Undoubtedly, TWRDS experience is a practical example of leveraging healthcare providers' decisions, care outcomes, and renovation.
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Fallo Renal Crónico , Diálisis Renal , Anciano , Humanos , Taiwán/epidemiología , Atención a la Salud , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , RiñónRESUMEN
Traumatic brain injury (TBI) is a silent epidemic that has been easily ignored. The safety and efficacy of restarting antiplatelet therapy after encountering traumatic brain injury (TBI) events remain a challenge. We explored the outcomes of restarting aspirin use on secondary stroke and mortality in patients with chronic stroke 4 weeks after suffering from a TBI episode in Taiwan. This study analyzed data from the National Health Insurance Research Database from January 2000 to December 2015. Overall, 136,211 individuals diagnosed with chronic stroke who suffered from acute TBI and received inpatient service were enrolled. The study outcomes were a competing risk of secondary stroke (ischemic and hemorrhagic) hospitalization and all-cause mortality. We identified a case group of 15,035 patients with chronic stroke (mean [SD] age of 53.25 [19.74] years; 55.63% male) who restarted aspirin use 4 weeks after suffering from TBI and a control group of 60,140 patients with chronic stroke (mean [SD] age of 53.12 [19.22] years; 55.63% male) who discontinued aspirin use after suffering from TBI. The risk of hospitalization of secondary ischemic stroke [adjusted hazard ratio (aHR) 0.694; 95% confidence interval (CI) 0.621-0.756; P < 0.001] and hemorrhagic stroke (aHR 0.642; 95% CI 0.549-0.723; P < 0.001) and all-cause mortality (aHR 0.840; 95% CI 0.720-0.946; P < 0.001) significantly decreased in patients with chronic stroke restarting aspirin use 1 month after suffering from TBI events (including intracranial hemorrhage) in comparison with the control subjects, regardless of those with or without diabetes mellitus, chronic kidney disease, myocardial infarction, atrial fibrillation, clopidogrel use, and dipyridamole use. Restarting aspirin use could lower the risks of secondary stroke (ischemic and hemorrhagic) hospitalization and all-cause mortality in patients with chronic stroke 1 month after suffering from TBI episodes.
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Lesiones Traumáticas del Encéfalo , Accidente Cerebrovascular , Humanos , Masculino , Adulto Joven , Adulto , Femenino , Aspirina/efectos adversos , Taiwán/epidemiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Hemorragia/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Quimioterapia Combinada , Daño Encefálico Crónico , Inhibidores de Agregación Plaquetaria/efectos adversosRESUMEN
BACKGROUND: Hemodialysis patients are at high risk of muscle loss as a result of aging and disease, and combined with inadequate dietary intake. The Healthy Eating Index for HemoDialysis patients (HEI-HD) was developed to assess the dietary quality of hemodialysis patients. The purposes of this study were to examine the effects of different nutritional education models using HEI-HD-based education on dietary quality and muscle mass in hemodialysis patients. METHODS: A quasi-experimental study was conducted from May 2019 to April 2021, with four groups, including no course for patients and nurses (Non-C), course for nurses (CN), course for patients (CP), and course for patients and nurses (CPN). The courses were delivered by registered dietitians. The data of 94 patients were collected and analyzed at baseline, after 2 months of intervention, and 2 months follow-up, including demographics, body composition, 3-day dietary records, and hemodialysis dietary knowledge. The HEI-HD index score was calculated. RESULTS: Patients aged 58.3 ± 10.1 years. The dietary quality change in the CPN group was improved as compared with the Non-C group (-3.4 ± 9.5 vs. 3.0 ± 5.5, 0.04). The skeletal muscle mass of the Non-C group at intervention was also significantly lower than baseline, but the CPN group was not. CONCLUSIONS: The HEI-HD-based nutritional education for both patients and nurses showed a positive effect on improving the dietary quality and maintaining muscle mass in hemodialysis patients.
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Dieta Saludable , Dieta , Humanos , Diálisis Renal/efectos adversos , Registros de Dieta , Músculos , Estado NutricionalRESUMEN
Introduction: End-stage kidney disease (ESKD) patients who need renal replacement therapy need to face a dialysis modality decision: the choice between hemodialysis (HD) and peritoneal dialysis (PD). Although the global differences in HD/PD penetration are affected by health-care policies, these two modalities may exert different effects on survival in patients with ESKD. Although Taiwan did not implicate PD as first policy, we still need to compare patients' outcomes using two modalities in a nation-wise database to determine future patients' care and health policies. Methods: We used the nationwide Taiwan Renal Registry Data System (TWRDS) database from 2005 to 2012 and included 52,900 patients (48,371 on HD and 4529 on PD) to determine all-cause and cardiovascular mortality among ESKD patients. Results: Age-matched survival probability from all-cause mortality was significantly lower in patients on PD than in those on HD (p < 0.05). The adjusted hazard ratios of 3-year and 5-year all-cause and cardiovascular mortality were significantly higher in PD compared with HD. The presence of comorbid conditions including myocardial infarction, coronary artery disease (CAD), diabetes mellitus (DM), hypoalbuminemia, hyperferritinemia and hypophosphatemia was related with significantly higher all-cause and CV mortality in PD patients. No significant difference was noted among younger patients <45 years of age regardless of DM and/or comorbid conditions. Conclusion: Although PD did not have the survival advantage compared to HD in all dialysis populations, PD was related with superior survival in younger non-DM patients, regardless of the presence of comorbidities. Similarly, for younger ESKD patients without the risk of CV disease, both PD and HD would be suitable dialysis modalities.
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The outcome of acute kidney injury (AKI) as a result of aminoglycosides (AGs) use remains uncertain in patients without prior chronic kidney disease (CKD). Therefore, we explored the outcomes of AGs use on AKI episodes associated with renal recovery and progress in patients without prior CKD in Taiwan. This was a retrospective cohort study by using the Taipei Medical University Research Database from January 2008 to December 2019. 43,259 individuals without CKD who had received parenteral AGs were enrolled. The exposed and unexposed groups underwent propensity score matching for age, gender, patients in intensive care unit/emergency admission, and covariates, except serum hemoglobin and albumin levels. We identified an exposed group of 40,547 patients who used AGs (median age, 54.4 years; 44.3% male) and an unexposed group of 40,547 patients without AG use (median age, 55.7 years; 45.5% male). There was the risk for AKI stage 1 (adjusted hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.00-1.79; p = 0.05) in patients that used AGs in comparison with the control subjects. Moreover, patients using AGs were significantly associated neither with the progression to acute kidney disease (AKD) stages nor with the progression to end-stage renal disease (ESRD) on dialysis. Further analyzed, there was an increased risk of AKI episodes for serum albumin levels less than 3.0 g/dL and hemoglobin levels less than 11.6 g/dL. Among patients without prior CKD, AGs-used individuals were associated with AKI risks, especially those at relatively low albumin (< 3.0 g/dL) or low hemoglobin (< 11.6 g/dL). That could raise awareness of AGs prescription in those patients in clinical practice.
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Lesión Renal Aguda , Insuficiencia Renal Crónica , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Aminoglicósidos/efectos adversos , Antibacterianos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Albúmina SéricaRESUMEN
While arteriovenous fistula (AVF) nonmaturation is a major issue of hemodialysis care, an effective treatment to improve AVF maturation remains lacking. AVF introduces pulsatile arterial blood flow into its venous limb and produces high luminal pressure gradient, which may have adverse effect on vascular remodeling. As such, the aim of the present study is to investigate effect of luminal pressure gradient on AVF nonmaturation. This single-center, prospective observational study includes patients receiving autologous AVF creation. Participants received early postoperative ultrasound 5-7 days after surgery to collect parameters including diameters, flow rates, and volume at inflow and outflow sites. Luminal pressure gradient was estimated by using modified Bernoulli equation. The outcome was spontaneous AVF maturation within 8 weeks after surgery without intervention. Thirty patients were included, of which the mean age was 66.9 years and 70% were male. At the end of study, 13 (43.3%) patients had spontaneous AVF maturation. All demographic and laboratory characteristics were similar between patients with mature and nonmature AVF. Regarding ultrasonographic parameters, nonmature AVF showed significantly higher inflow/outflow diameter ratio, inflow velocity, and luminal pressure gradient. While these 3 parameters were significantly correlated, multivariate logistic regression showed their significant association with AVF nonmaturation. Receiver operating characteristic curve exhibited their high predictive value for AVF nonmaturation. Our findings showed that higher inflow/outflow ratio, inflow velocity, and AVF luminal pressure gradient in early postoperative ultrasound predicted risk of AVF nonmaturation. Reducing inflow/outflow diameter ratio or inflow rate may be an approach to improve AVF maturation. The predictive value of this early assessment might have impact on the clinical practice of AVF care.
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Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Anciano , Fístula Arteriovenosa/etiología , Derivación Arteriovenosa Quirúrgica/efectos adversos , Femenino , Humanos , Masculino , Estudios Prospectivos , Diálisis Renal , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Venas/diagnóstico por imagenRESUMEN
Cardiovascular disease (CVD) is the most common complication in hemodialysis patients. Nutritional education provided by dietitians could improve overall dietary quality and dietary fat quality to reduce the risk of CVD. However, no studies have investigated the relationship between dietary fat quality (using the hypocholesterolemic/hypercholesterolemic ratio, or the h/H) and CVD risk factors in hemodialysis patients. The aim of this study was to examine the association between the h/H and CVD risk factors, and further explore how nutritional education intervention models could improve dietary fat quality and CVD risk factors in hemodialysis patients. A quasi-experimental design was conducted from May 2019 to April 2021 on four groups, including 'no course for patients and nurses' as the non-C group, a "course for nurses" as the CN group, a "course for patients" as the CP group, and a "course for patients and nurses" as the CPN group. Nutritional education booklets based on a healthy eating index for hemodialysis patients were developed and provided to patients and nurses. Data of 119 patients were collected at baseline, intervention, and follow-up periods, including patients' basic information, blood biochemical data, dietary content, and calculated h/H. The results showed that the h/H was negatively correlated with body mass index (BMI) and positively correlated with high-density lipoprotein cholesterol (HDL-C). Compared with the non-C group, the CPN group was significantly higher in the h/H as well as HDL-C, and significantly lower in serum total cholesterol. In conclusion, the h/H was found to predict CVD risk factors, which helps in improving dyslipidemia. Nutritional education for both patients and nurses showed a beneficial impact on reducing CVD risks in hemodialysis patients.
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Enfermedades Cardiovasculares , Grasas de la Dieta , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , HDL-Colesterol , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Diálisis Renal/efectos adversos , Factores de RiesgoRESUMEN
Rationale & Objective: Taiwan implemented national pay-for-performance programs for chronic kidney disease (CKD) care in 2006 and 2011; however, it is unknown whether this affected trends in maintenance dialysis. This study assessed the temporal trends in the incidence, prevalence, and mortality of individuals treated with maintenance dialysis from 2002-2016 in Taiwan. Study Design: Follow-up study using Taiwan Renal Disease System Databases. Setting & Participants: Participants who received dialysis for ≥90 days. Predictors: Age, sex, and calendar year. Outcomes: Incidence, prevalence of maintenance dialysis, or death, ascertained using the National Death Registry database. Analytical Approach: The estimated annual percentage change was assessed by a generalized linear model, and the association of the programs with changes in the incidence of maintenance dialysis was evaluated using an age-period-cohort model. Results: A total of 144,258 incident cases with a follow-up of 346 million person-years were analyzed during the observed periods. The estimated annual percentage change of the expected crude incidence rate was slightly reduced by 0.41% (95% CI, -1.06 to 0.24) and was more obvious in women and patients aged greater than 70 years; whereas, it was significantly increased in those aged greater than 75 years. After disentangling age and cohort effects, the implementation of the care programs was associated with an overall net drift of -1.09% (95% CI, -1.65 to -0.52) per year and a significant linear reduction in the period rate ratio from 1.06 (95% CI, 1.02-1.09) in the years 2002-2006 to 0.95 (95% CI, 0.92-0.98) in 2012-2016, using years 2007-2011 as reference. Limitations: The findings of the study may have limited inferences to other countries with different health care systems. Conclusions: The implementation of universal CKD care programs in Taiwan has significantly reduced the long-term trends in the incidence of maintenance dialysis; hence, devoting governmental resources to CKD care and prevention is advocated.
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Laxatives are commonly prescribed for constipation management; however, they are recognized as an independent factor associated with cardiovascular diseases. Arteriovenous fistula (AVF) is the closest to the ideal model of hemodialysis (HD) vascular access and part of the cardiovascular system. Our study aims to explore the association of contact laxative use with AVF maturation outcomes in patients undergoing HD. We conducted a multi-center cohort study of 480 contact laxative users and 472 non-users who had undergone initial AVF creation. All patients were followed until the outcomes of AVF maturation were confirmed. Multivariable logistic regression models were performed to evaluate the risk of AVF maturation failure imposed by laxatives. Here, we found that patients who used contact laxatives were significantly associated with an increased risk of AVF maturation failure compared to non-users (adjusted odds ratio, 1.64; p = 0.003). Notably, the risk of AVF maturation failure increased when increasing their average daily doses and cumulative treatment days. In conclusion, our study found a significant dose- and duration-dependent relationship between contact laxative use and an increased risk of AVF maturation failure. Thus, laxatives should be prescribed with caution in this population. Further studies are needed to validate these observations and investigate the potential mechanisms.
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Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Fallo Renal Crónico , Fístula Arteriovenosa/etiología , Derivación Arteriovenosa Quirúrgica/efectos adversos , Estudios de Cohortes , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Laxativos/uso terapéutico , Diálisis Renal , Estudios RetrospectivosRESUMEN
Acute kidney disease (AKD) comprises acute kidney injury (AKI). However, whether the AKD staging system has prognostic values among AKI patients with different baseline estimated glomerular filtration (eGFR) remains a controversial issue. Algorithm-based approach was applied to identify AKI occurrence and to define different AKD stages. Risk ratio for major adverse kidney events (MAKE), including (1) eGFR decline > 35% from baseline, (2) initiation of dialysis, (3) in-hospital mortality of different AKD subgroups were identified by multivariable logistic regression. Among the 4741 AKI patients identified from January 2015 to December 2018, AKD stages 1-3 after AKI was common (53% in the lower baseline eGFR group and 51% in the higher baseline eGFR group). In the logistic regression model adjusted for demographics and comorbidities at 1-year follow-up, AKD stages 1/2/3 (AKD stage 0 as reference group) were associated with higher risks of MAKE (AKD stage: odds ratio, 95% confidence interval [95% CI], AKD 1: 1.85, 1.56-2.19; AKD 2: 3.43, 2.85-4.12; AKD 3: 10.41, 8.68-12.49). Regardless of baseline eGFR, staging criteria for AKD identified AKI patients who were at higher risk of kidney function decline, dialysis and mortality. Post-AKI AKD patients with severer stage need intensified care and timely intervention.
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Lesión Renal Aguda , Diálisis Renal , Enfermedad Aguda , Femenino , Mortalidad Hospitalaria , Humanos , Riñón , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic adipose tissue-derived stem cells (ADSCs) among chronic kidney disease (CKD) patients. 12 eligible CKD patients with an estimated glomerular filtration rate (eGFR) of 15-44 ml/min/1.73 m2 received one dose of intravenous allogeneic ADSCs (ELIXCYTE® ), as 3 groups: 3 low dose (6.4 × 107 cells in total of 8 ml), 3 middle dose (19.2 × 107 cells in total of 24 ml) and 6 high dose (32.0 × 107 cells in total of 40 ml) of ELIXCYTE® and evaluated after 48 weeks. Primary endpoint was the safety profiles in terms of incidence of adverse events (AEs) and serious adverse event (SAE). Two subjects in high dose group experienced a total of 2 treatment-related AEs which are Grade 1 slow speech and Grade 1 bradyphrenia after the infusion. One subject in middle dose group experienced an SAE unlikely related to treatment, grade 2 proteinuria. No fatal AE was reported in this study. An increase in eGFR was observed in 7 out of 12 subjects (58%) at Week 24 and in 6 of 12 subjects (50%) by Week 48. By Week 24, an increase in eGFR by more than 20% among all CKD patients with baseline eGFR ⧠30 ml/min/1.73 m2 as compared to only 2 subjects in baseline eGFR < 30 ml/min/1.73 m2 group. No significant reduction in proteinuria was noted among all subjects. This phase I trial demonstrated single-dose intravenous ELIXCYTE was well tolerated in moderate-to-severe CKD patients and its preliminary efficacy warrants future studies.
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Trasplante de Células Madre Hematopoyéticas , Insuficiencia Renal Crónica , Tejido Adiposo , Estudios de Factibilidad , Femenino , Humanos , Masculino , Insuficiencia Renal Crónica/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Severe vascular damage and complications are often observed in cancer patients during treatment with chemotherapeutic drugs such as cisplatin. Thus, development of potential options to ameliorate the vascular side effects is urgently needed. In this study, the effects and the underlying mechanisms of far-infrared radiation (FIR) on cisplatin-induced vascular injury and endothelial cytotoxicity/dysfunction in mice and human umbilical vein endothelial cells (HUVECs) were investigated. An important finding is that the severe vascular stenosis and poor blood flow seen in cisplatin-treated mice were greatly mitigated by FIR irradiation (30 minutes/day) for 1-3 days. Moreover, FIR markedly increased the levels of phosphorylation of PI3K and Akt, and VEGF secretion, as well as the expression and the activity of hypoxia-inducible factor 1α (HIF-1α) in cisplatin-treated HUVECs in a promyelocytic leukemia zinc finger protein (PLZF)-dependent manner. However, FIR-stimulated endothelial angiogenesis and VEGF release were significantly diminished by transfection with HIF-1α siRNA. We also confirmed that HIF-1α, PI3K, and PLZF contribute to the inhibitory effect of FIR on cisplatin-induced apoptosis in HUVECs. Notably, FIR did not affect the anticancer activity and the HIF-1α/VEGF cascade in cisplatin-treated cancer cells under normoxic or hypoxic condition, indicating that the actions of FIR may specifically target endothelial cells. It is the first study to demonstrate that FIR effectively attenuates cisplatin-induced vascular damage and impaired angiogenesis through activation of HIF-1α-dependent processes via regulation of PLZF and PI3K/Akt. Taken together, cotreatment with the noninvasive and easily performed FIR has a therapeutic potential to prevent the pathogenesis of vascular complications in cancer patients during cisplatin treatment.
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Cisplatino , Endotelio Vascular , Subunidad alfa del Factor 1 Inducible por Hipoxia , Rayos Infrarrojos , Fosfatidilinositol 3-Quinasas , Enfermedades Vasculares , Animales , Cisplatino/efectos adversos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/efectos de la radiación , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de la radiación , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Rayos Infrarrojos/uso terapéutico , Ratones , Neovascularización Patológica/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Enfermedades Vasculares/inducido químicamente , Enfermedades Vasculares/radioterapia , Factor A de Crecimiento Endotelial Vascular/metabolismoAsunto(s)
Enfermedades Renales , Salud Pública , Femenino , Humanos , Incidencia , Masculino , Políticas , Prevalencia , Taiwán/epidemiologíaAsunto(s)
Insuficiencia Renal Crónica , Femenino , Humanos , Masculino , Insuficiencia Renal Crónica/terapia , TaiwánRESUMEN
BACKGROUND: Arteriovenous fistula (AVF) is the most important vascular access for hemodialysis; however, preventive treatment to maintain the patency of AVFs has not been developed. In endothelium, ß-catenin functions in both the intercellular adherens complex and signaling pathways that induce the transition of endothelial cells to myofibroblasts in response to mechanical stimuli. We hypothesize that mechanical disturbances in the AVF activate ß-catenin signaling leading to the transition of endothelial cells to myofibroblasts, which cause AVF thickening. The present study aimed to test this hypothesis. METHODS: Chronic kidney disease in mice was induced by a 0.2% adenine diet. AVFs were created by aortocaval puncture. Human umbilical vein endothelial cells (HUVECs) were used in the cell experiments. A pressure-culture system was used to simulate mechanical disturbances of the AVF. RESULTS: Co-expression of CD31 and smooth muscle alpha-actin (αSMA), loss of cell-cell adhesions, and the expression of the myofibroblast marker, integrin subunit ß6 (ITGB6), indicated transition to myofibroblasts in mouse AVF. Nuclear translocation of ß-catenin, decreased axin2, and increased c-myc expression were also observed in the AVF, indicating activated ß-catenin signaling. To confirm that ß-catenin signaling contributes to AVF lesions, ß-catenin signaling was inhibited with pyrvinium pamoate; ß-catenin inhibition significantly attenuated AVF thickening and decreased myofibroblasts. In HUVECs, barometric pressure-induced nuclear localization of ß-catenin and increased expression of the myofibroblast markers, αSMA and ITGB6. These changes were attenuated via pretreatment with ß-catenin inhibition. CONCLUSIONS: The results of this study indicate that mechanical disturbance in AVF activates ß-catenin signaling to induce the transition of endothelial cells to myofibroblasts. This signaling cascade can be targeted to maintain AVF patency.